Stress Management and Biomarkers of Risk in Cardiac Rehabilitation

Coronary Heart Disease Clinical Trial

— ENHANCED  

Official title:

Enhancing Standard Cardiac Rehabilitation With Stress Management Training in Patients With Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00981253
• Other study ID #: Pro00015896
• Secondary ID: R01HL093374-01A2
• Status: Completed
• Phase: N/A
• First received: September 21, 2009
• Last updated: January 8, 2018
• Start date: September 2009
• Est. completion date: February 2016

Study information

• Verified date: January 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the extent to which combining exercise and stress management training (SMT) is more effective at improving biomarkers in vulnerable cardiac patients compared to exercise-based cardiac rehabilitation alone.

Description:

Coronary heart disease (CHD) is the leading cause of death in the United States and in roughly half the cases its first clinical manifestations, myocardial infarction (MI) or sudden cardiac death (SCD), are fatal. There is considerable evidence that "stress" plays a significant and independent role in the occurrence of CHD and its complications. This evidence has provided the rationale for developing interventional strategies to reduce stress in susceptible individuals in order to modify the natural history of these clinical events. There are now promising data to suggest that stress management training (SMT) is one such approach, and that SMT can have beneficial effects on psychosocial and medical outcomes. However, many of the randomized clinical trials (RCTs) employing stress management approaches in CHD patients have had important methodological limitations and several of the larger RCTs have failed to demonstrate a benefit for SMT over usual care, raising questions about the value of SMT for patients with CHD. Reliance on "hard" clinical endpoints is problematic because studies require such large sample sizes that they are logistically difficult to conduct and are prohibitively expensive. The use of intermediate pathophysiologic endpoints that have been shown independently to be associated with increased risk represents a novel and exciting opportunity to examine the added value of SMT in exercise-based cardiac rehabilitation (CR) compared to CR without SMT on key biomarkers of risk in vulnerable CHD patients.

This 12-week study will enroll adults with stable CHD who are eligible for CR. Participants will be randomly assigned to either standard cardiac rehabilitation or standard cardiac rehabilitation enhanced with weekly SMT. Prior to randomization, medical screening, standardized psychosocial questionnaires, mental stress testing, assessment of diet and physical activity, and exercise testing will be conducted. Additional biomarkers of risk will be assessed through measures of flow-mediated vasodilation, inflammation, platelet function, stress hormones, baroreflex, and heart rate variability.

Participants assigned to CR alone will engage in supervised exercise routines 3 times per week. Participants will be encouraged to maintain consistent exercise duration and effort throughout each session. Participants assigned to CR enhanced with SMT will engage in standard exercise-based cardiac rehabilitation and also receive weekly group SMT. At the conclusion of the 12-week intervention, participants will return for repeat assessments of stress and biomarker measures. At 6 months, 12 months, and annually up to 4 years participants will be contacted for information regarding major adverse cardiovascular events, other medical events and medication use.

Additionally a group of age, gender, and disease matched cardiac patients referred to CR, during the same time interval, but who elected not to participate in CR will form a non-randomized comparison group for cardiac events.

Overall, 164 participants were consented for study participation at Duke University Medical Center. Of these, 151 participants were randomized to either Standard Cardiac Rehabilitation or Enhanced Cardiac Rehabilitation. Post-intervention assessments were completed on 145 participants; 151 participants were available for intention-to-treat analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: February 2016
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Coronary Heart Disease (CHD)

• Eligibility for Cardiac Rehabilitation (CR) in North Carolina

• Capacity to give informed consent and follow study procedures

Exclusion Criteria:

• Received heart transplant

• LVEF < 30%

• Labile ECG changes prior to testing

• Currently using a pacemaker

• Resting BP > 200/120 mm Hg

• Left main disease > 50%

• Unable to comply with assessment procedures

• Unwilling or unable to be randomized to treatment groups

• Primary diagnosis of the following psychiatric disorders: schizophrenia, dementia, current delirium, or other psychotic disorder

• Current alcohol or substance abuse disorder

• Acute suicide risk

• Actively undergoing ongoing psychiatric treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Behavioral:
• SMT-enhanced Cardiac Rehabilitation
Standard exercise-based cardiac rehabilitation, three times per week, enhanced with weekly stress management training for 12 weeks.
• Standard Cardiac Rehabilitation
Supervised exercise, three times per week, for 12 weeks.

Locations

Country	Name	City	State
United States	University of North Carolina Hospitals - Meadowmont	Chapel Hill	North Carolina
United States	Duke University Medical Center - Center for Living	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (9)

Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12):892-902. Review. — View Citation

Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, Franklin B, Sanderson B, Southard D; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Nursing; American Heart Association Council on Epidemiology and Prevention; American Heart Association Council on Nutrition, Physical Activity, and Metabolism; American Association of Cardiovascular and Pulmonary Rehabilitation. Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2007 May 22;115(20):2675-82. Epub 2007 May 18. — View Citation

Blumenthal JA, Babyak M, Wei J, O'Connor C, Waugh R, Eisenstein E, Mark D, Sherwood A, Woodley PS, Irwin RJ, Reed G. Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol. 2002 Jan 15;89(2):164-8. — View Citation

Blumenthal JA, Jiang W, Babyak MA, Krantz DS, Frid DJ, Coleman RE, Waugh R, Hanson M, Appelbaum M, O'Connor C, Morris JJ. Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med. 1997 Oct 27;157(19):2213-23. — View Citation

Blumenthal JA, Sherwood A, Babyak MA, Watkins LL, Waugh R, Georgiades A, Bacon SL, Hayano J, Coleman RE, Hinderliter A. Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial. JAMA. 2005 Apr 6;293(13):1626-34. — View Citation

Frasure-Smith N, Lespérance F, Prince RH, Verrier P, Garber RA, Juneau M, Wolfson C, Bourassa MG. Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction. Lancet. 1997 Aug 16;350(9076):473-9. — View Citation

Jones DA, West RR. Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial. BMJ. 1996 Dec 14;313(7071):1517-21. — View Citation

Rees K, Bennett P, West R, Davey SG, Ebrahim S. Psychological interventions for coronary heart disease. Cochrane Database Syst Rev. 2004;(2):CD002902. Review. Update in: Cochrane Database Syst Rev. 2011;(8):CD002902. — View Citation

Wenger NK, Froelicher ES, Smith LK, Ades PA, Berra K, Blumenthal JA, Certo CM, Dattilo AM, Davis D, DeBusk RF, et al. Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute. Clin Pract Guidel Quick Ref Guide Clin. 1995 Oct;(17):1-23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Composite Stress Score	A global stress measure (mean rank), was the primary outcome combining the following components at baseline and following treatment: Beck Depression Inventory II, Spielberger Anxiety Inventory-State, General Health Questionnaire, PROMIS Anger Questionnaire, and Perceived Stress Scale. A range from 1 to 147 was present with higher scores suggestive of better function. The change in each individual scaled score is presented in primary outcome 2.	Baseline; 12 weeks
Primary	Change From Baseline to 12 Weeks in Individual Scaled Scores	Beck Depression Inventory II: 21-item scale used to measure depression. Scores range from 0 to 63, with higher scores suggesting greater depressive symptoms.; State-Trait Anxiety Inventory: 20-item scale which assess levels of state anxiety. Scores range from 20 to 80 with scores =40 suggesting clinically significant anxiety.; General Health Questionnaire:12-item measure of general distress. Scores range from 0 to 36, with higher scores indicating greater emotional distress.; Patient-Reported Outcomes Measurement Information System (PROMIS) Anger: 8-item scale which assesses anger. Scores range from 8 to 40, with higher scores indicating greater anger.; Perceived Stress Scale: 10-item measure of general distress and perceived ability to cope. Scores range from 0 to 40, higher scores indicate greater stress.	Baseline; 12 weeks
Secondary	Major Adverse Cardiovascular Events (MACE) - All Cause Death, MI, Cardiac Revascularization and Cardiovascular Hospitalization.	Patients documented all medical encounters on an annual basis after enrollment. Medical records were reviewed, and events, categorized on the basis of American College of Cardiology/American Heart Association criteria. The following medical events were included: all-cause mortality, fatal and nonfatal myocardial infarction (MI), coronary or peripheral artery revascularization, stroke/transient ischemic attack, and unstable angina requiring hospitalization.	Baseline through Follow-up (median, 3.2 years)
Secondary	Change in High-sensitivity C-Reactive Protein	High-sensitivity C-reactive protein was quantified by ELISA. Values >10 mg/L were truncated at 10 to account for acute inflammatory processes that may have skewed the distribution of this blood marker.	Baseline; 12 weeks
Secondary	Heart Rate Variability During Controlled Breathing (HRV-DB)	Heart rate variability was obtained from beat-to-beat heart rate. Heart rate was assessed from R-R interval changes elicited during a 100-second controlled breathing task.	At 12 weeks
Secondary	Baroreflex Sensitivity	Baroreflex sensitivity was obtained from beat-to-beat heart rate and blood pressure recorded from patients in the supine position with a Nexfin noninvasive blood pressure monitor.	At 12 weeks
Secondary	Heart Rate Variability During Rest	Heart rate variability was obtained from beat-to-beat heart rate. Heart rate was assessed from R-R interval changes elicited during 5 minutes of normal relaxed breathing	At 12 weeks